In order for the symptoms of withdrawal to occur, one must have first developed a form of drug dependence. This may occur as physical dependence, psychological dependence or both. Drug dependence develops from consuming one or more substances over a period of time. Dependence arises in a dose-dependent manner and produces withdrawal symptoms that vary with the type of drug that is consumed.

For example, prolonged use of an antidepressant medication is likely to cause a much different reaction when discontinued compared to discontinuation of an opioid, such as heroin. Withdrawal symptoms from opiates include anxiety, sweating, vomiting, and diarrhea. Alcohol withdrawal symptoms include irritability, fatigue, shaking, sweating, and nausea. Withdrawal from nicotine can cause irritability, fatigue, insomnia, headache, and difficulty concentrating. Many prescription and legal nonprescription substances can also cause withdrawal symptoms when individuals stop consuming them, even if they were taken as directed by a physician.

The route of administration, whether intravenous, intramuscular, oral or otherwise, can also play a role in determining the severity of withdrawal symptoms. There are different stages of withdrawal as well; generally, a person will start to feel bad (crash or come down), progress to feeling worse, hit a plateau, and then the symptoms begin to dissipate. However, withdrawal from certain drugs (barbiturates, benzodiazepines, alcohol, glucocorticoids) can be fatal. While it is seldom fatal to the user, withdrawal from opiates (and some other drugs) can cause miscarriage, due to fetal withdrawal. The term “cold turkey” is used to describe the sudden cessation use of a substance and the ensuing physiologic manifestations.

The symptoms from withdrawal may be even more dramatic when the drug has masked prolonged malnutrition, disease, chronic pain, infections (common in intravenous drug use), or sleep deprivation, conditions that drug abusers often suffer as a secondary consequence of the drug. When the drug is removed, these conditions may resurface and be confused with withdrawal symptoms.

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Homeostasis is impacted in many ways by drug usage and withdrawal. Homeostasis is the body’s ability to maintain a certain chemical equilibrium in both the brain and throughout the body. For example, when we get cold and get chills/shiver that is our body trying to make its own heat in order to keep our internal temperature inside right around 98 degrees Fahrenheit. The internal systems try to perpetuate homeostasis by using different counter-regulatory methods in order to create a new state of balance based on the presence of the drug in the system [1]. These methods include adapting the body’s levels of neurotransmitters, hormones, and other substances present to adjust for the addition of the drug to the body [2]. In reference to drug addiction and withdrawal, we see the chemical makeup of the brain being changed as the substances are continuously ingested. Continuous over-stimulation makes it difficult for the brain to balance itself out [2]. Once someone has altered their chemical make-up we see shifts in priorities and lack of interest in things that may have once excited them. Once the individual has reached a state of extreme dysregulation to where it cannot recover, allostasis has dropped to a point that would normally be considered a state of illness [3]. Now that the brain has reached this new chemical make-up we start to see a downwards spiral of the individual. We see normal methods used by homeostasis (counter-adaptation, sensitization, etc) now being used outside of their normal range [3].

After an individual becomes addicted, their only concern is when and how they are going to get that next pill. We see the role of sensitaztion being used in drug addiction to create more of a need for the drug each time that it is used [3]. Often times there is a shift causing over-activity of dopamine creating a break in homeostasis [1]. This leads to the phenomenon known as tolerance. As the individual continues abusing, they will need more amounts of the drug to achieve the original high they once had. The body will keep adjusting itself to maintain homeostasis, so as the abuse continues the level of tolerance rises [2]. This is often where we see issues concerning overdose. Many young people use drugs are used to dull whatever pain that they are already dealing with, so it allows for a desensitized view to develop which can then transcend into family/school/work life.If they are desensitized, they do not care about what they are doing to themselves or others. When a person stops taking the drugs, the bodily systems are then unprepared to maintain homeostasis. This leads to an imbalance in neurotransmitters, hormones and affects many other systems as well [2]. This is what leads to “dopesickness” or as many others refer to it, the symptoms of withdrawal. Symptomatology can vary based on the individual and the drug being abused. Each drug has notorious symptoms that it is known for, but each individual with have a highly personalized experience when going through withdrawals.

As noted above, many drugs should not be stopped abruptly[8] without the advice and supervision of a physician, especially if the medication induces dependence or if the condition they are being used to treat is potentially dangerous and likely to return once medication is stopped, such as diabetes, asthma, heart conditions and many psychological or neurological conditions, like epilepsy, hypertension, schizophrenia and psychosis. With careful physician attention, however, medication prioritization and discontinuation can decrease costs, simplify prescription regimens, decrease risks of adverse drug events and poly-pharmacy, focus therapies where they are most effective, and prevent cost-related under-use of medications.[9]

^Nestler EJ (December 2013). “Cellular basis of memory for addiction”. Dialogues Clin. Neurosci. 15 (4): 431–443. PMC3898681. PMID24459410. Despite the importance of numerous psychosocial factors, at its core, drug addiction involves a biological process: the ability of repeated exposure to a drug of abuse to induce changes in a vulnerable brain that drive the compulsive seeking and taking of drugs, and loss of control over drug use, that define a state of addiction. … A large body of literature has demonstrated that such ΔFosB induction in D1-type [nucleus accumbens] neurons increases an animal’s sensitivity to drug as well as natural rewards and promotes drug self-administration, presumably through a process of positive reinforcement … Another ΔFosB target is cFos: as ΔFosB accumulates with repeated drug exposure it represses c-Fos and contributes to the molecular switch whereby ΔFosB is selectively induced in the chronic drug-treated state.41. … Moreover, there is increasing evidence that, despite a range of genetic risks for addiction across the population, exposure to sufficiently high doses of a drug for long periods of time can transform someone who has relatively lower genetic loading into an addict.

^“Glossary of Terms”. Mount Sinai School of Medicine. Department of Neuroscience. Retrieved 9 February 2015.

^Volkow ND, Koob GF, McLellan AT (January 2016). “Neurobiologic Advances from the Brain Disease Model of Addiction”. N. Engl. J. Med. 374 (4): 363–371. doi:10.1056/NEJMra1511480. PMID26816013. Substance-use disorder: A diagnostic term in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) referring to recurrent use of alcohol or other drugs that causes clinically and functionally significant impairment, such as health problems, disability, and failure to meet major responsibilities at work, school, or home. Depending on the level of severity, this disorder is classified as mild, moderate, or severe.Addiction: A term used to indicate the most severe, chronic stage of substance-use disorder, in which there is a substantial loss of self-control, as indicated by compulsive drug taking despite the desire to stop taking the drug. In the DSM-5, the term addiction is synonymous with the classification of severe substance-use disorder.